A silent disease, even with normal blood tests

Fatty liver disease is one of those conditions that most often progresses without any noticeable warning sign. This is what makes it both common and underdiagnosed.

In the United States, where about one adult in three is thought to be affected, studies show the vast majority of affected people are unaware of their condition. In France, of the millions of people probably affected, only a small fraction have received a diagnosis. Most cases of fatty liver disease are discovered incidentally, during an abdominal ultrasound done for another reason. At the global level, MASLD still doesn't appear in the World Health Organization's (WHO) major health action plans, a gap many hepatologists point out.

The absence of symptoms, the rule rather than the exception

In the vast majority of cases, fatty liver disease causes no symptoms at all, even at already advanced stages. When signs do appear, they remain vague and nonspecific: unusual fatigue, mild discomfort in the upper right abdomen. These signals are easily attributed to something else. This lack of a clear symptom is exactly why so many people are unaware they are affected.

The reason for this silence lies in the nature of the liver. It has little internal nerve supply: only its outer capsule is sensitive to pain, when the organ swells. It also has considerable functional reserve. It keeps performing its functions, such as filtering blood, producing proteins, or storing energy, even when a significant portion of its cells is damaged. The signs that reveal serious liver disease generally appear only at the advanced cirrhosis stage: jaundice, abdominal swelling, bleeding, confusion. At that stage, options are far more limited.

Certain indirect signs can, however, point the way, without being specific. These include brown, velvety patches in the folds of the neck or armpits, called acanthosis nigricans, which reflect insulin resistance. An increased waist circumference and elevated triglycerides are others. These are less symptoms of the liver itself than signals of the metabolic backdrop that promotes fatty liver disease.

Normal blood test results don't rule out the disease

A frequently misunderstood point: liver enzymes (AST, ALT), blood markers usually associated with liver health, can remain perfectly normal even in the presence of significant fatty liver disease. A reassuring standard liver panel alone therefore isn't enough to rule out the diagnosis. This is exactly why scores calculated from several combined markers offer a better risk estimate than looking at each value in isolation. That's the case with FIB-4, which combines age, liver enzymes, and platelet count.

Liver enzymes are proteins contained in liver cells that leak into the blood when those cells are damaged. They therefore reflect liver distress at a given moment, not the amount of fat or the degree of fibrosis. A landmark American study, the Dallas Heart Study, showed as early as 2004 that nearly 80% of people with steatosis measured by imaging had normal liver enzymes. Another paradox: as fibrosis progresses toward cirrhosis, the number of remaining cells decreases, and liver enzymes can even drop. Laboratory “normal ranges” that are sometimes too broad also contribute to abnormalities going unnoticed.

FIB-4 partly works around these limits. Its formula multiplies age by AST, then divides the result by the product of platelet count and the square root of ALT. Each element has its own logic. Fibrosis risk rises with age. As fibrosis progresses, AST tends to rise more than ALT. And platelets decrease in advanced forms, as the spleen retains more of them. A result below 1.3 makes advanced fibrosis very unlikely, with about 90% reliability for ruling it out. A result above 2.67 makes it likely and warrants a specialist opinion. In between lies a gray zone, which calls for further testing. After age 65, the lower threshold is raised to 2.0, since age mechanically raises the score. Conversely, FIB-4 is less reliable before age 35.

Ultrasound, an often-necessary complement

For people with metabolic risk factors (diabetes, obesity, hypertension), a liver ultrasound remains the first-line exam for confirming fatty liver disease, alongside a blood score like FIB-4. The latter mainly indicates the risk of fibrosis already present, rather than the mere presence of fat in the liver.

Ultrasound has its own limits. It reliably detects moderate or significant steatosis, but can miss mild steatosis, when less than about 20% of cells contain fat. Above all, it can't reliably assess the degree of fibrosis.

This is why the 2024 European guidelines propose a two-step pathway. First, FIB-4, calculated from a simple blood draw. Then, if it isn't reassuring, a measurement of liver stiffness by elastography, the best known being FibroScan. This painless test takes about ten minutes and resembles an ultrasound. It measures liver stiffness, which rises the more fibrosis is present, and can also estimate fat content. A result below 8 kPa is reassuring. A high result leads to specialized care. Liver biopsy, once essential, is now reserved for cases where noninvasive tests can't reach a conclusion.

Why early screening makes a real difference

Contrary to a common belief, fatty liver disease caught early, before advanced fibrosis sets in, generally remains reversible with appropriate lifestyle changes. This topic is covered in this blog's last article. It's this reversibility, unique to early stages, that makes screening especially valuable: the earlier the detection, the wider the range of options remains.

Screening also has value beyond the liver. Discovering fatty liver disease often leads to checking for undetected early diabetes, hypertension, or sleep apnea. For people with advanced fibrosis, regular follow-up makes it possible to catch complications early, particularly liver cancer, at a stage when it can still be treated effectively.

Who should consider screening

People with one or more metabolic risk factors (type 2 diabetes, overweight or obesity, hypertension, abnormal cholesterol) have a particular interest in assessing their fatty liver disease risk, even with no symptoms at all, precisely because the absence of symptoms doesn't allow for filtering who needs it.

The 2024 European guidelines prioritize three groups. The first is people with type 2 diabetes. The second, people who are overweight or obese with at least one other metabolic risk factor. The third, people with abnormal liver enzymes. To these should be added people with a close relative who had cirrhosis, and those who combine metabolic risk factors with regular alcohol consumption. Alcohol and metabolism do, in fact, add their effects on the liver. The hub's Is my alcohol consumption risky? test can help assess this second factor.

In practice, the elements needed to calculate FIB-4 are often already on a routine blood panel: liver enzymes and platelet count. All that's needed is to enter them into the tool, then discuss the result with your primary care doctor.

To estimate your own risk level, take the “Do I have fatty liver disease?” test.